Diseases of the circulatory system including the heart, heart valves and blood vessels are the biggest cause of deaths of adults worldwide. Among them, blood vessel-associated diseases such as arteriosclerosis, angina, myocardial infarction and stroke are the most prevalent.
According to the statistics of the World Health Organization (WHO), it is estimated that about 12 million people die of cardiovascular diseases every year and, in the US, about 57 million people are receiving treatments for one or more cardiovascular diseases. The related cost is reported to amount to 260 billion dollars a year.
Primary therapies for cardiovascular disease include autologous blood vessel implantation or methods of using auxiliary devices for opening the blood vessel such as a stent. Autologous blood vessel implantation is mostly employed in obstructive vascular diseases caused by arteriosclerosis and is often used in genetic fibrosis disorder, aortic aneurysm, aortic dissection, arteritis, aortic injury, etc. Grafts that may be used for autologous blood vessel implantation are very limited such as the internal mammary artery, lumbar artery, ulnar artery, etc. Also, since available vein grafts are limited, autologous blood vessel implantation requiring repeated surgery may be difficult or impossible. Accordingly, to save or improve the quality of life of patients, allogenic blood vessels or artificial blood vessels capable of replacing the autologous blood vessels are required.
At present, artificial blood vessels made of poly(ethylene terephthalate) or polytetrafluoroethylene (PTFE) are used as implantable artificial blood vessels. However, these artificial blood vessels are applicable only to large inner diameters exceeding 6 mm. It is because they can be blocked by small blood clots formed on the inner surface of the blood vessels.
If the blood vessels are narrow with an inner diameter of not greater than 6 mm, even small blood clots may block the blood vessels and lead to fatal results. To solve this problem, blood clot formation on the inside wall of the blood vessel should be prevented. Associated methods include a tissue engineering method of inoculating ordinary cells or stem cells to a biodegradable, blood vessel-shaped support and growing the cells, a method of attaching only the vascular endothelial cells that prevent blood clot formation on the inner surface of a biodegradable or non-degradable support, or a method of attaching heparin, warfarin or a negatively charged functional group without using cells. However, the method using vascular endothelial cells has difficulty in that the handling of the vascular endothelial cells is not easy. And, although the method of using heparin, etc. is somewhat effective in the early stage, blood clots are formed with time. Accordingly, the need on new practical materials capable of replacing blood vessels is ever increasing.
Meanwhile, stainless steel or titanium alloy is frequently used to make a stent. If the blood vessel wall is damaged by such material, smooth muscle cells may grow at the wound site and block the blood vessel. Also, blood platelets tend to aggregate on the surface of the material, thus forming blood clots and blocking the blood vessel. In order to prevent such unwanted tissue capsulation or blood clotting, negatively charged functional groups are attached on the surface of the stent or drugs such as cyclosporin A are used. However, these methods are problematic in that the blood vessel is blocked again as time goes by.
Korean Patent No. 0661396 discloses an anti-thrombogenic stent coated with multiple layers in which hydrophobic heparin polymers are distributed in the upper layer. The stent is applicable to blood vessels with large inner diameters but not to those with small inner diameters. In addition, since it exhibits weak hydrophobicity, proteins, blood platelets, etc. may be easily attached to the surface of the stent through hydrophobic interaction.
Accordingly, an artificial blood vessel or a stent which is applicable to blood vessels with small and large inner diameters and is capable of minimizing blood clot formation is needed.